Complimentary and alternative medicines (CAM) are amongst the most commonly used therapies worldwide and in the US for chronic liver diseases. Silymarin, the active ingredient of the milk thistle, Silybum marianum, is one of the commonest used herbal medications but its efficacy in chronic liver disease is unproven. Liver disease secondary to both hepatitis C (HCV) and non-alcoholic steatohepatitis (NASH) represent 2 of the commonest liver diseases in the US and there is a need for the study of silymarin in these diseases in a controlled clinical trial. We are proposing three collaborative clinical trials to evaluate silymarin versus placebo in HCV patients who have never received treatment, in HCV patients who have failed treatment and in patients with NASH. These will be double blind, placebo controlled phase l/ll trials focusing on dose finding, safety and efficacy of silymarin. The endpoints of the trials will include histological improvement in liver disease and multiple secondary surrogate markers to understand both how silymarin works and to get a preliminary idea of the endpoints to be utilized in larger Phase 3 trials. We also intend to evaluate important secondary factors such as expectations of patients on CAM and effect of silymarin on quality of life. The goal of these studies is to determine whether there is a rationale for larger Phase 3 studies of silymarin in patients with chronic liver disease. [unreadable] [unreadable] [unreadable]